STRUCTURAL BIOLOGY CORE 1 . MAIN OBJECTIVES AND NEW DIRECTIONS The use of Structural Biology on the La Jolla Torrey Pines Mesa has increased tremendously over the past 5 years. For example, BIMR has added 4 new faculty members as major users of its Structural Biology Facility and is directed by crystallography Robert Liddington. However, presently this Core is part of the Burnham NIH-funded Cancer Center with little or no access to neuroscientists on the La Jolla Torrey Pines Mesa. Additionally, two faculty at The Salk are also heavily invested in crystallography but heretofore were not organized as a Core and thus have little interaction with neuroscientists. Moreover, the Head of NMR at UCSD, Stan Opella, is world-renowned in this area and has an NMR facility that would be made available to neuroscientists on this grant as a satellite core. Hence, the structural core will function with headquarters at BIMR and satellite facilities at The Salk Institute and UCSD. This Structural Core will foster collaborative interactions by allowing equal access to neuroscientists. BIMR has made major investments in instrumentation for structural biology, including the acquisition of three new NMR spectrometers and upgrades for the X-ray diffraction set up. UCSD has installed a state-or-the-art 900 MHz spectrometer, which will be available for collaborations of neuroscientists. Scientific progress has been impressive in the recent past by these facilities, including 6 papers in the journals Cell, Science and Nature that utilized structural data from the facilities. However, Neuroscientists have had minimal, if any, access to the faculty or instrumentation because they are located within the Cancer Centers at BIMR, TSRI, UCSD, and The Salk. The current grant will rectify this by making the facility and the faculty available to Neuroscientists as a Core Unit. In summary, the Structural Biology Core comprises two facilities: Crystallography and NMR. Scientific, logistical, and budgetary issues provide justification for this merger of services. The primary application of Crystallography and NMR overlap, and most research projects require both Crystallography and NMR. The merged facility serves the needs of users with a broad range of expertise. There are several neuroscience investigators who are not mainstream structural biologists but who have a desire to learn structural techniques. The facility provides appropriate training and direction for these people. Other "hardcore" structural groups require much less support, and the facility will primarily supply the necessary hardware and technical support to achieve the scientific goals. One manager (who is free to this grant) oversees both techniques within the Structural Biology Facility and provides the necessary training (in conjunction with the faculty supervisors);technicians paid for by the current grant will coordinate the efforts at the three centers (BIMR, Salk, UCSD, and facilitate TSRI neuroscientist access as well). Future plans include a protein expression facility in this Core.